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Serotonin release measured in the human brain: a PET study with [11C]CIMBI-36 and d-amphetamine challenge

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  • David Erritzoe
  • Abhishekh H Ashok
  • Graham E Searle
  • Alessandro Colasanti
  • Samuel Turton
  • Yvonne Lewis
  • Mickael Huiban
  • Sara Moz
  • Jan Passchier
  • Azeem Saleem
  • John Beaver
  • Anne Lingford-Hughes
  • David J Nutt
  • Oliver D Howes
  • Roger N Gunn
  • Gitte M Knudsen
  • Eugenii A Rabiner
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Positron emission tomography (PET) enables non-invasive estimation of neurotransmitter fluctuations in the living human brain. While these methods have been applied to dopamine and some other transmitters, estimation of 5-hydroxytryptamine (5-HT; Serotonin) release has proved to be challenging. Here we demonstrate the utility of the novel 5-HT2A receptor agonist radioligand, [11C]CIMBI-36, and a d-amphetamine challenge to evaluate synaptic 5-HT changes in the living human brain. Seventeen healthy male volunteers received [11C]CIMBI-36 PET scans before and 3 h after an oral dose of d-amphetamine (0.5 mg/kg). Dynamic PET data were acquired over 90 min, and the total volume of distribution (VT) in the frontal cortex and the cerebellum derived from a kinetic analysis using MA1. The frontal cortex binding potential (BPNDfrontal) was calculated as (VTfrontal/VTcerebellum) - 1. ∆BPNDfrontal = 1 - (BPNDfrontal post-dose/BPNDfrontal baseline) was used as an index of 5-HT release. Statistical inference was tested by means of a paired Students t-test evaluating a reduction in post-amphetamine [11C]CIMBI-36 BPNDfrontal. Following d-amphetamine administration, [11C]CIMBI-36 BPNDfrontal was reduced by 14 ± 13% (p = 0.002). Similar effects were observed in other cortical regions examined in an exploratory analysis. [11C]CIMBI-36 binding is sensitive to synaptic serotonin release in the human brain, and when combined with a d-amphetamine challenge, the evaluation of the human brain serotonin system in neuropsychiatric disorders, such as major depression and Parkinson's disease is enabled.

Original languageEnglish
JournalNeuropsychopharmacology
Volume45
Issue number5
Pages (from-to)804-810
Number of pages7
ISSN0893-133X
DOIs
Publication statusPublished - Apr 2020

ID: 60077328